Treatment success high in stable RA despite steroid tapering
Glucocorticoid therapy can be safely tapered while maintaining high treatment success rates in patients with rheumatoid arthritis (RA) who had achieved disease control on tocilizumab, at the cost of a slight loss of disease control, suggests a randomized study presented at the EULAR 2019 Congress.
“On the basis of our results, we believe that all patients achieving low disease activity or remission with tocilizumab should be offered glucocorticoid tapering,” said lead investigator Professor Gerd Burmester from the Department of Rheumatology and Clinical Immunology at Charité – University Medicine Berlin in Berlin, Germany.
Approximately two-thirds of the patients (65 percent) who underwent glucocorticoid tapering achieved treatment success, defined as fulfilling all three criteria of DAS28-ESR* ≤3.2 at week 24, no RA flare during the study course of 24 weeks, and no adrenal insufficiency necessitating replacement therapy. [EULAR 2019, abstract OP0030]
Similarly, patients randomized to continue glucocorticoid treatment also had high rate of treatment success after 24 weeks (77 percent, relative risk [RR], 0.83; p=0.021 vs glucocorticoid tapering).
There was also a small but significant difference of 0.6 DAS28-ESR (p<0.001) between the two arms at 24 weeks, in favour of glucocorticoid continuation.
“The 0.6 DAS28-ESR unit between-arm difference should be interpreted in the context of approximately two-thirds of tapered patients experiencing treatment success and no tapered patients discontinuing due to lack of flare control,” Burmester pointed out.
Flares occurred in 26 percent of the patients who tapered glucocorticoid therapy and in 11 percent of those who continued the therapy. Of these patients, only one discontinued blinded treatment in the study due to insufficient flare control, which occurred in the glucocorticoid continuation group.
In addition, no patients experienced symptomatic adrenal insufficiency, which according to the researchers, indicates that “the taper schedule was safe regarding adrenal insufficiency.”
Serious adverse events were reported in 5 percent of the patients who continued glucocorticoids and 3 percent of those who tapered glucocorticoid therapy.
Participants in the study were 259 patients with RA who were treated with tocilizumab and taking glucocorticoids with or without csDMARDs for at least 24 weeks. Patients with low disease activity (DAS28-ESR <3.2) or in remission for at least 4 weeks while being on stable doses of tocilizumab and csDMARD were randomized to continue glucocorticoid therapy (prednisone 5 mg/day) or undergo tapering (from 4 mg/day to completely stopping glucocorticoids at weeks 16–24, with a 1 mg reduction every 4 weeks).
While the efficacy of glucocorticoid therapy in patients with RA is well established, guidelines have recommended that glucocorticoids be used for only a short term and the therapy be tapered, ideally, within 3–6 months. Long-term use of glucocorticoids, particularly prednisone-equivalent doses of >5 mg/day, is discouraged due to potential side effects such as osteoporosis, diabetes, cardiovascular disease, and infections. [Ann Rheum Dis 2017;76:960-977; Arthritis Rheum 2016;68:1-26]
“The risk to benefit profile of glucocorticoid therapy in RA is very controversial,” said Professor John Isaacs, Chairperson of the EULAR Abstract Selection Committee. “We welcome these data to inform our understanding in this area and ultimately the better management of patients suffering with this disease.”
“The results suggest that all patients achieving low disease activity or remission with tocilizumab and receiving long-term low-dose glucocorticoids should be considered for glucocorticoid tapering, ideally targeting discontinuation,” Burmester concluded.